Association between ustekinumab trough concentrations and biochemical outcomes in patients with Crohn�s disease. A real life study

Espín, Rosa Gómez; Prado, Isabel Nicolás de; Candel, M Gil; Carrión, Marta González; Redondo, Lorena Rentero; Navalón, Carles Iniesta

doi:10.17235/reed.2020.7124/2020

Cited by 9 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Statements that reached consensus regarding the role of reactive TDM are presented in Table 1. Supportive text for these statements (1-9) is provided in Supplementary Digital Content 2 (http://links.lww.com/AJG/C133) (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

Section: Reactive Tdmmentioning

confidence: 99%

“…Regarding biologics other than anti-TNF therapies, the only data supporting the role of proactive TDM currently derive exclusively from exposure-response relationship studies showing that higher vedolizumab and ustekinumab concentrations are associated with better therapeutic outcomes (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44).…”

Section: Proactive Tdmmentioning

confidence: 99%

See 1 more Smart Citation

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

et al. 2021

View full text Add to dashboard Cite

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1–10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10–15 μg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti–tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti–tumor necrosis factors.

show abstract

Section: Reactive Tdmmentioning

confidence: 99%

Section: Proactive Tdmmentioning

confidence: 99%

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Reactive ustekinumab TDM, however, has been suggested to be performed in nonresponders at the end of induction and in patients with a secondary loss of response during maintenance treatment [28]. Also, three real-world studies show association between ustekinumab trough concentrations and clinical outcomes [16,29,30]. However, the data on ustekinumab TCs related to dose intensification and their relationship to clinical outcomes is limited.…”

Section: Discussionmentioning

confidence: 99%

“…Our results are comparable to those reported by Verstockt et al [29], where the mean ustekinumab TC was 2.6 mg/mL at 16 weeks. A threshold of 1.9 mg/mL at 24 weeks for endoscopic response and 2.2 mg/mL for composite clinical/biochemical remission was suggested in real-world studies [16,29].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to efficacy, safety and treatment persistence, concomitant medication use, and treatment immunogenicity remain as crucial factors for decisions on dose optimization. In the IM-UNITI trial, approximately one-third of the study patients received concomitant immunosuppressants [3].The available data, however, do not offer clear guidance for the combination therapy with ustekinumab, although the proportion of antiustekinumab antibodies (AUAs) were equally low in patients on ustekinumab monotherapy and those on combination therapy [14].The low immunogenicity and a clear exposure-response relationship in ustekinumab trough concentrations (TCs) have been reported separately in realworld and clinical studies including ulcerative colitis [3,4,15,16]. However, real-world data on ustekinumab TCs and immunogenicity are scarce among dose-optimized patients.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

Sipponen

Björkesten

Hallinen

et al. 2021

Scandinavian Journal of Gastroenterology

View full text Add to dashboard Cite

Background: Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. Methods: Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. Results: Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. Conclusions: Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification.

show abstract

Physiologically-based pharmacokinetic modeling to predict the exposure and provide dosage regimens of Ustekinumab in pediatric patients with inflammatory bowel disease

Cai,

Wu,

Guo

et al. 2024

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Association between ustekinumab trough concentrations and biochemical outcomes in patients with Crohn�s disease. A real life study

Cited by 9 publications

References 24 publications

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

Physiologically-based pharmacokinetic modeling to predict the exposure and provide dosage regimens of Ustekinumab in pediatric patients with inflammatory bowel disease

Contact Info

Product

Resources

About